The overall objective of this research is to investigate the endocrine regulation of cell differentiation and of progesterone synthesis in the corpus luteum of the rat and rabbit. Specifically, the physiological role of the theca lutein cell and the role of estrogen and of LH in the differentiation of the granulosa lutein cell will be emphasized. Two basic approaches, recently developed in this laboratory, will be used. First, transplants of luteinizing granulosa cells or of luteinizing whole follicles will be made into hypophysectomized Fischer 344 rats and in rabbits. Second, granulosa lutein cells from rabbits will be studied in monolayer cultures. The following hypotheses will be tested: 1) androgen (or its aromatized derivative) and prolactin are necessary for increased steroidogenic capacity and further differentiation of rat granulosa lutein cells in the second week after ovulation; 2) an important role of the theca lutein cell is its participation in luteal estrogen synthesis, which is stimulated by LH (rat); 3) the small steroidogenic cell population in rat and rabbit corpora lutea is derived from thecal cells of the follicle; 4) the role of LH in the rabbit corpus luteum is to stimulate the recruitment or differentiation of small luteal cells, suspected to be of thecal origin; 5) differentiation and progesterone synthesis by granulosa lutein cells in culture can be stimulated either by LH or by estradiol; the steroidogenic effect of estradiol is mediated by 3'5' - cyclic AMP (rabbit). These studies are expected to lead to new understanding of the interactions between cell populations in the corpus luteum and of the hormones that govern the normal function and regression of the corpus luteum.